Serial change in myocardial tissue Doppler imaging from fetus to neonate.

BACKGROUND: Our goal was to evaluate the serial change in myocardial performance from fetus to neonate using tissue Doppler imaging (TDI). METHOD AND RESULTS: There were 37 term infants in the present study. The TDI sensor was placed at the level of the lateral mitral annulus (M-TDI), inter-ventricular septum (IVS-TDI) and the lateral tricuspid annulus (T-TDI). We measured TDI parameters from fetus to neonate. On univariate analysis, E' (cm/s), A' (cm/s), and S' (cm/s) of three ventricular walls of TDI parameters excluding E' IVS-TDI significantly decreased during the transition from fetal to neonatal circulation. E'/A' ratio, E/E' ratio and myocardial performance index (MPI) of three ventricular walls of TDI parameters excluding T-TDI MPI significantly increased during the transition from fetal to neonatal circulation. When multiple linear regression analysis with a step-wise procedure during the transition from fetus to neonate for TDI parameters was applied to variables, significant differences were noted for predicting decreases in M-TDI S' (6.55 to 3.97, p < 0.001) and IVS-TDI A', (6.69 to 4.69, p < 0.001), and increases in IVS-TDI E'/A' ratio (0.77 to 1.02, p < 0.001) and IVS-TDI E/E' ratio (8.25 to 13.65, p < 0.001). CONCLUSION: In conclusion, we found that the myocardial performances of both ventricles decreased during the transition from fetus to neonate using TDI parameters. In particular, left ventricular systolic performance was affected more than when fetal circulation changed to neonate circulation. Our findings suggest that serial change in TDI can give new information to estimate myocardial performance of the neonate.

Association of abdominal aortic wall thickness in the newborn with maternal factors.

PURPOSE: The goal of the present study is to carry out prospective echocardiographic measurements of intima-media thickness (IMT) in the abdominal artery of newborns. METHODS: Study subjects were 96 mothers and their newborns. We measured the adjusted IMT (aIMT, mm/mm) of newborn abdominal arteries by high-resolution ultrasound and evaluated the association of aIMT with various maternal and newborn factors. RESULTS: Negative correlations were observed between aIMT and gestational age (r = - 0.678, p < 0.01) and positive correlations between aIMT and placenta-to-fetus weight ratio (r = 0.418, p < 0.01). Comparing the small-for-gestational-age (SGA) versus appropriate-for-gestational-age (AGA) categories, aIMT in the SGA (n = 14) was greater than in the AGA (n = 82), with values of [0.115 (0.117) mm/mm versus 0.084 (0.074) mm/mm, p < 0.01], respectively. A multiple linear regression analysis was performed with aIMT as a dependent variable, and significant correlations were noted with gestational age (R2 = 0.524, ß = - 0.515, p < 0.001 for gestational age). CONCLUSION: On the basis of these findings, we suggest that aIMT thickness is associated with placenta-to-fetus weight ratio and gestational age, and that increased values of aIMT in SGA may indicate presence of a latent link to cardiovascular disease that might otherwise go undetected in infancy.

Morphogenic protein epimorphin protects intestinal epithelial cells from oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt signals.

Epimorphin is a mesenchymal protein that regulates morphogenesis of epithelial cells. Our preliminary study suggested a novel function of epimorphin in enhancing survival of intestinal epithelial cells (IEC). Oxidative stress leads to cell injury and death and is suggested to be a key contributor to pathogenesis of inflammatory bowel disease. This study was conducted to determine whether epimorphin protects IEC from oxidative stress. Rat intestinal epithelial cell line IEC-6 was cultured with epimorphin (10 and 20 mug/ml), and the life span of IEC was assessed. The mean life span of IEC-6 cells was prolonged 1.9-fold (P < 0.0006) by treatment with epimorphin. We then examined the epimorphin signaling pathways. Epimorphin phosphorylated epidermal growth factor (EGF) receptor, activated the MEK/extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and phosphatidylinositol 3 (PI3) kinase/Akt pathways, phosphorylated Bad, and induced Bcl-X(L) and survivin. Hydrogen peroxide (1 mM) induced cell death in 92% of IEC-6 cells, but epimorphin dramatically diminished (88.7%) cell death induced by hydrogen peroxide (P < 0.0001). This protective effect of epimorphin was significantly attenuated by inhibitors of MEK and PI3 kinase (P < 0.0001) or EGF receptor-neutralizing antibody (P = 0.0007). In wound assays, the number of migrated cells in the wound area decreased (72.5%) by treatment with 30 muM hydrogen peroxide, but epimorphin increased the number of migrated cells 3.18-fold (P < 0.0001). These results support a novel function of epimorphin in protecting IEC from oxidative stress. This anti-oxidative function of epimorphin is dramatic and is likely mediated by the activation of EGF receptors and the MEK/extracellular signal-regulated kinase and PI3 kinase/Akt signaling pathways and through the induction of anti-apoptotic factors.

Sucralfate prevents the delay of wound repair in intestinal epithelial cells by hydrogen peroxide through NF-kappaB pathway.

BACKGROUND: Recent studies have shown that sucralfate (SF) has therapeutic effects on colonic inflammation in ulcerative colitis. The aim of this study was to clarify the function of SF for wound repair in intestinal epithelial cells (IEC). METHODS: (1) Activation of signal proteins [ERK1/2 mitogen-activated protein kinase (MAPK), IkappaB-alpha] in IEC-6 cells after stimulation with 10(-4) M potassium sucrose octasulfate (SOS), which is the functional element of SF, was assessed by Western blot. (2) Induction of transforming growth factor (TGF)-beta1, TGF-alpha, EGF, and cyclooxygenase-2 (COX-2) mRNA after stimulation of IEC-6 cells with SOS was assessed by reverse transcriptase-polymerase chain reaction. (3) IEC-6 cells were wounded and cultured for 24 h with various concentrations of SOS in the absence or presence of 20 microM H(2)O(2). Epithelial migration or proliferation was assessed by counting migrating cells or bromodeoxyuridine (BrdU)-positive cells across the wound border. RESULTS: (1) SOS activated IkappaB-alpha, but it did not activate ERK1/2 MAPK. (2) SOS enhanced the expression of COX-2 mRNA, but it did not change the mRNA expression of other growth factors. (3) SOS did not enhance wound repair in IEC-6 cells, but it decreased the number of dead cells (maximum, 74%) (P < 0.01) in a dose-dependent manner and prevented the diminishment of epithelial migration (maximum, 61%) (P < 0.01) and proliferation (maximum, 37%) (P < 0.05) induced by H(2)O(2). These functions of SOS were suppressed by the NF-kappaB and COX-2 inhibitors. CONCLUSIONS: SOS prevented the delay of wound repair in IEC-6 cells induced by H(2)O(2), probably through induction of COX-2 and an anti-apoptotic mechanism. These effects of SOS might be given through the activation of the NF-kappaB pathway.

[Long-term prognosis of the patients of myotonic dystrophy with tube feeding].

We studied the long-term prognosis of the patients of myotonic dystrophy with tube feeding. Subjects were 51 patients (31 male patients and 20 female patients) of typical myotonic dystrophy who were at least once admitted in our hospital. We examined the age of the introduction of tube feeding, the cause of the introduction, respiratory and motor ability at the introduction, the duration of tube feeding, the cause of death and the extension of CTG repeats in the patients. Comparing with the patients with tube feeding and the patients without it, we also examined the prognosis after the introduction of tube feeding. Tube feeding was introduced in 13 cases. The mean age of tube feeding was 57.9 +/- 8.3 years old. The mean age of death of non tube feeding group was 55.9 +/- 5.5 years old. These show tube feeding was introduced in more elderly patients. Statstically the tube feeding was effective, but poor prognosis even after the introduction of tube feeding was suggested because the mean survival time after the introduction was about 850 days. We could not find any correlation between the age of the introduction of tube feeding and the extension of CAG report.

[The results of surgical treatment for pseudomyxoma peritonei].

The surgical results of 37 patients with pseudomyxoma pertonei are reported. Twenty eight patients received laparotomy and complete cytoreduction (CC-0) could be done in 6 patients. However, 13 patients received incomplete cytoreduction, and 9 patients underwent drainage of ascites and peritoneal washing. The Peritoneal Carcinomatosis Index (PCI) was less than 20 in CC-0 patients. CC-0 patients survived significantly better than patients with residual disease. Accordingly, peritoneal washing to remove free cancer cells should be aimed for complete cytoreduction of the solid mucinous nodules.

Novel evidence suggesting Clostridium difficile is present in human gut microbiota more frequently than previously suspected.

Prevalence rate of Clostridium difficile in healthy human adults is believed to be very low. Our RT-PCR system using glass powder, which can eliminate PCR inhibitors, detected C. difficile toxin B mRNA in 16 of 30 fecal samples (53.3%) from healthy human adults. In contrast, we failed to detect toxin B in the same fecal samples by PCR using DNA templates extracted with phenol-chloroform. Our results suggest that PCR inhibitors in feces carried through phenol-chloroform extraction procedure might suppress the sensitivity of PCR and that C. difficile is actually present in human gut microbiota more frequently than previously suspected.

Altered expression of epimorphin in ulcerative colitis.

BACKGROUND AND AIM: Epimorphin is suggested to play a key role in the morphogenesis of epithelial cells. We focused on epimorphin and attempted to clarify the relationship between expression of this molecule and inflammatory bowel disease (IBD). METHODS: Colonic specimens were taken from 23 patients with ulcerative colitis (UC), 15 with Crohn's disease (CD), six with non-IBD colitis, and 10 normal controls. Distribution and expression of epimorphin protein were examined by immunohistochemistry and western blot analysis, and expression of epimorphin messenger (m)RNA by reverse transcription-polymerase chain reaction. Distribution of basic fibroblast growth factor (bFGF) was also examined by immunohistochemistry. RESULTS: In the normal colonic mucosa, epimorphin was observed around the epithelial cells, in some fibroblasts, vascular endothelial cells, and macrophages. In UC patients, epimorphin around epithelial cells disappeared or decreased, and the number of epimorphin-containing cells (mean + standard error/mm2) was significantly increased in active UC patients (1550.8 +/- 144.2) compared with patients in remission (692.8 +/- 45.8), CD patients (790.0 +/- 31.2), non-IBD colitis patients (710.8 +/- 29.2), and controls (664.8 +/- 39.6) (P < 0.01). The number of bFGF-containing cells was significantly increased in active UC and CD patients compared with UC patients in remission, CD and non-IBD colitis patients, and controls (P < 0.05 or P < 0.01). Total expression of epimorphin protein and mRNA was increased in the active stage of UC. Expression of the 34 kDa epimorphin isoform decreased or disappeared in 20 out of 23 cases of UC. CONCLUSION: Our results suggest that altered expression of epimorphin contributes to impaired healing and chronic inflammation in the colonic mucosa of UC patients.

Systemic and local evidence of increased Fas-mediated apoptosis in ulcerative colitis.

BACKGROUND AND AIMS: Recent studies suggest that Fas-mediated apoptosis is involved in the pathogenesis of inflammatory bowel disease (IBD). This study was conducted to clarify whether soluble forms of Fas (sFas) and Fas ligand (sFasL) are concerned with inflammation in IBD. METHODS AND PATIENTS: Concentration of serum sFas and sFasL was measured by enzyme-linked immunosorbent assay in 10 patients with ulcerative colitis (UC), 10 with Crohn's disease (CD) in both active and remission stages, and 20 controls. Expression of Fas and sFas in colonic mucosa was examined by western blot. Distribution of Fas and FasL in colonic mucosa was examined by immunohistochemistry in 20 UC, 20 CD, and 10 non-IBD colitis patients and in 10 controls. Apoptotic cells were examined by TUNEL. RESULTS: Concentration of systemic sFas was significantly lower in active UC than controls. The number of FasL-containing cells was significantly higher in active UC than in remission UC, non-IBD colitis, and controls. Apoptotic cells were increased in active UC. CONCLUSIONS: Our results demonstrate that systemic and local Fas-mediated apoptosis is promoted in UC, which might be involved in the pathogenesis in UC.